Pan Chang-yu

The kidney expression of matrix metalloproteinase-9 in the diabetic nephropathy of Kkay mice

BACKGROUND Disorder of the extracellular matrix has been suggested to play a role in the development of diabetic nephropathy. The aim of the present study was to examine the expression of matrix metalloproteinase-9 (MMP-9) in the kidney of Kkay mice, a type 2 diabetic model. METHODS Eight Kkay control mice (KA) and eight Kkay diabetic mice (KB) were fed with the same diets for 4 months and sacrificed after glucose levels and weight were measured. The renal pathological changes were examined by periodic acid-Schiff and periodic acid-silver methenamine staining, and the glomerulosclerosis indexes (GIs) were calculated. The levels of MMP-9 protein in the kidney tissue were assessed by immunohistochemistry. The gene expression of MMP-9 was measured by reverse transcription polymerase chain reaction. RESULTS The diabetic group had morphological findings of diabetic nephropathy, and their GI (240.0+/-17.3) was much higher than that of the control group (118.4+/-15.1) (P<.01). The mean positive area of MMP-9 protein in the glomeruli of Kkay mice in the KB group was higher than that in the KA group. The expression of MMP-9 messenger RNA level in the diabetic KB group was up-regulated when compared with the KA group. CONCLUSION The expression of MMP-9 in the kidney of mice with diabetic nephropathy was enhanced, and MMP-9 might be involved in the development of diabetic nephropathy.

Effects of plasma homocysteine levels on serum HTase/PON activity in patients with type 2 diabetes

IntroductionHomocysteine is a predictor of vascular disease and may have an important role in diabetes. In this study, we examined the effects of folic acid and methylcobalamin supplementation on changes in homocysteine (Hcy) levels and homocysteine thiolactonase/paraoxonase (HTase/PON) activity in a short-term trial.MethodsNinety patients with type 2 diabetes were randomly divided into three groups: Group I received no vitamin supplementation, group II received 5 mg/day folic acid (orally), group III received folic acid (5 mg/day) in combination with methylcobalamin (500 μg/day; intramuscularly, on prescription). All patients were treated for 2 weeks. Plasma Hcy, HTase/PON activity, vitamin B12, and folic acid were measured before and after supplementation in each group. In addition, forty healthy (nondiabetic) controls were enrolled.ResultsSerum HTase/PON activity was significantly higher in diabetics compared with controls, plasma Hcy levels were significantly lower (P<0.05). After vitamin supplementation there was a significant reduction in plasma Hcy levels. The mean percentage reduction in Hcy was 2.75% in group I, 14% in group II and 37.3% in group III. There was a significant inverse correlation between the changes in HTase/PON activity and Hcy levels (r=−0.29, P=0.004). A 2.72% increase in HTase/PON activity was seen in group I, an 8.03% increase was detected when folic acid was given in group II (P<0.001), and a 17.59% increase in HTase/PON activity was seen in group III (P<0.001).ConclusionShort-term oral folic acid (5 mg/day) supplementation with or without methylcobalamin appeared to be an effective approach to decrease Hcy levels and increase HTase/PON activity in patients with type 2 diabetes. A decrease in plasma Hcy levels may partly account for the elevation of serum HTase/PON activity. This could be a novel mechanism to protect against vascular diabetic complications.

Effects of telmisartan on lipid metabolisms and proinflammatory factors secretion of differentiated 3T3-L1 adipocytes

Aim: To investigate the effect of telmisartan on the lipometabolisms and the proinflammatory factors secreted from 3T3-L1 adipocytes and to explore the possible mechanisms. Materials and methods: Telmisartan was applied to interfere with mature 3T3-L1 adipocytes. The culture’s free fatty acids, interleukin 6 (IL-6) and tumor necrosis factor α (TNFα) were evaluated. Oil Red O staining was used to determine the adipogenesis of 3T3-L1 adipocytes. 18F-FDG uptake levels corrected for protein content were determined by cellular radioactivity. The total RNA was isolated for hybridization experimentation in the microarray. Results: Telmisartan reduced lipid storage and increased 18F-FDG uptake in a dose-dependent manner, reduced the levels of IL-6 and TNFα and increased those of free fatty acids. One hundred and fifty-seven differentially expressed genes were found by microarray. The mitogen-activated protein kinase (MAPK) signaling pathway involved in the secretion of proinflammatory factor and lipid metabolisms was affected by telmisartan. The expression of endothelial nitric oxide synthetase gene 3 (Nos3) and carnitine palmitoyl transferase 1α (CPT1α) was up-regulated by telmisartan. Conclusions: Telmisartan affected lipometabolisms and the proinflammatory factors secreted from adipocytes. Nos3, CPT1α and the MAPK pathway being affected by telmisartan may be the underlying cause of the improvement in lipid metabolisms and secretion of proinflammatory factors of differentiated 3T3-L1 adipocytes.